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carbonyl group on C8 formed two hydrogen bonds with Ser170 and Tyr183 . Even so, emodin did not form a hydrogen bond with NADP as did the ligand within the crystal structure. Instead, emodin formed hydrophobic contacts with the NADP . Moreover, residues Leu126, Val227 and Tyr177 were involved within the hydrophobic contacts with emodin . Emodin inhibited Angiogenesis inhibitor 11b HSD1 activity in vivo The in vivo efficacy of emodin at inhibiting 11b HSD1 activity was evaluated in C57BL 6J mice. Two hours after p.o. administration of 100 or 200 mg?kg 1 emodin, the mice were killed, and also the liver and mesenteric fat were removed and assayed for 11b HSD1 activity. As shown in Figure 2, oral administration of 100 or 200 mg?kg 1 of emodin considerably inhibited liver 11b HSD1 enzymatic activity by 17.6 and 31.
3 and mesenteric fat 11b HSD1 enzymatic activity by 21.5 and 46.7 , respectively. The results demonstrate Angiogenesis inhibitor that emodin inhibits 11b HSD1 activity in vivo. Emodin antagonized insulin resistance induced by glucocorticoids It is effectively documented that prolonged exposure to elevated glucocorticoid levels produces insulin resistance, a hallmark of diabetes mellitus. Dexamethasone is a synthetic active glucocorticoid, which has a powerful affinity for the GR, whereas prednisone is a synthetic cortisone analogue, which has little affin ity for the GR. Even so, prednisone may be catalysed by the liver 11b HSD1 to convert it into its active metabolite, prednisolone, which has reasonably high glucocorticoid activity.
The insulin tolerance test showed that therapy of C57BL 6J mice with dexamethasone or prednisone for 14 days reduced the glucose lowering effect in response towards the insulin challenge, indicating the presence of insulin resistant . When concurrently treated with 100 or 200 mg?kg 1 emodin, the glucose lowering effects after GW0742 insulin injection were elevated in prednisone treated mice, which suggests improved insulin sensitivity. In contrast, the insulin resistance induced by dexamethasone was not improved by the concurrent therapy with 200 mg?kg 1 emodin . These outcomes indicate that emodin can reverse prednisone , but not dexamethasoneinduced insulin resistance in mice, which confirms its inhibitory effect on 11b HSD1 in vivo. Emodin improved metabolic abnormalities of DIO mice C57BL 6J mice fed a high fat diet program developed moderate obesity, mild hyperglycaemia, dyslipidaemia and insulin resistance.
Emodin administered by oral gavage b.i.d. for 7 days reduced fasting glucose concentrations to 77.2 on the vehicle manage mice, and these remained considerably reduce throughout the therapy period . Following 24 days of therapy with emodin, the PARP DIO mice exhibited a substantial reduction in blood glucose levels at all time points following oral glucose challenge . This was accompanied by a reduction in serum insulin concentrations GW0742 at 15, 30 and 60 min after glucose loading within the 100 mg?kg 1 emodintreated mice . Treatment with emodin for 28 days also evoked a considerably greater reduction in blood glucose values 40 and 90 min after insulin injection , indicating an improved insulin tolerance in emodin treated DIO mice . Moreover, the serum insulin level was also considerably reduced, to 66.
2 of manage mice, after 35 days of therapy with 100 mg?kg 1 emodin . Emodin also improved the lipid profiles in DIO mice. Following 35 days of therapy with 100 mg?kg 1 emodin, the serum triglyceride and total cholesterol levels were considerably reduced by 19.3 and 12.5 , respectively, compared with Angiogenesis inhibitors vehicle manage mice . Emodin also brought on a 22.7 reduction of NEFA level, although this did not reach statistical significance . Chronic therapy with emodin lowered body weight and appetite in DIO mice. DIO mice treated with 100 mg?kg 1 emodin showed a steady decline in body weight that GW0742 was considerably distinct from vehicle treated animals from day 18 on the therapy; their body weights were reduced by 13.9 at the end of therapy .
Emodin also GW0742 affected the animals’ feeding behaviour, resulting in a 17 reduction in food intake compared with the vehicle treated animals . Moreover, it brought on a preferential reduction in mesenteric fat pad and perirenal fat pad weights by 29 and 47 , respectively. The subcutaneous fat weight in emodin treated DIO mice was reduced compared with vehicle treated manage mice , however it basically had no effect on epididymal fat weight . Emodin suppressed 11b HSD1 activity and reduced the mRNA levels of gluconeogenic genes in DIO mice The enzymatic activity of 11b HSD1 in liver and adipose tissues was measured 35 days after the therapy of DIO mice with 100 mg?kg 1 emodin. A substantial decrease in 11b HSD1 activity was observed in both the liver and mesenteric adipose tissues of emodin treated DIO mice . The 11b HSD1 activity in liver and mesenteric adipose tissues was decreased by 53.5 and 41.2 , respectively, whereas no substantial change in 11b HSD1 mRNA expression was observed . Treatment of DIO mice with 100 mg?kg 1